This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Binding of S-protein to ACE2 in enterocytes induces ACE2 dysregulation leading to gut dysbiosis
Point of Contact
- Laure-Alix Clerbaux
- Julija Filipovska
- Cataia Ives
|Author status||OECD status||OECD project||SAAOP status|
|Under development: Not open for comment. Do not cite||Under Development||1.96||Included in OECD Work Plan|
This AOP was last modified on July 16, 2022 18:37
|Binding to ACE2||May 17, 2022 10:20|
|Dysregulation, ACE2 expression and activity||December 05, 2021 12:24|
|Gut microbiota, alteration||January 04, 2022 10:31|
|Binding to ACE2 leads to ACE2 dysregulation||February 12, 2022 08:14|
|ACE2 dysregulation leads to Gut dysbiosis||December 02, 2021 07:16|
S-protein binding to ACE2 receptor induces dysregulation of ACE2 physiological functions in the intestines such as modulation of the local renin-angiotensin signaling (RAS) system (10.1152/ajpgi.00099.202) or as a chaperone for dietary amino acid (AA) transporters in the intestines, such as the tryptophan transporter B0AT1 (Slc6a19) (10.1042/CS20200477; 10.1053/j.gastro.2008.10.055). The gastrointestinal RAS appears to be involved in numerous processes in the gut including AA, fluid and electrolyte absorption and secretion (10.1111/j.1365-2036.2011.04971.x.). Besides, the gut microbiota is influenced by the host intestinal AA metabolism as gut bacteria use dietary AA for protein synthesis (10.1038/s41598-020-74122-9).
AOP Development Strategy
AOP428 is developed as a part of the CIAO project, "Modelling the Pathogenesis of COVID-19 Using the Adverse Outcome Pathway (AOP)". The overall goal is to organize and understand the vast amount of data that is constantly evolving as a result of the COVID-19 pandemic and identify uncertainties and knowledge gaps that may be missing using the AOP framework. Many AOPs were developed in the CIAO project, each AOP focusing on a specific element of the SARS-COV-2 virus responses in humans.
AOP428 focuses on the intestinal part and alteration of the gut microbiota via ACE2 dysregulation.